The goal of this research is to evaluate the validity of telomere length as a biomarker of physiological dysregulation or allostatic load (AL) [cumulative wear and tear on physiological systems and organs due to adversity] in children. An assortment of biomarkers currently exists to measure components of AL across a variety of different physiological systems. Each of these measures has limitations in collection and interpretation, especially in children where the biologic effects of AL may not yet be detectable. Consequently, very few studies have focused on biological risk of AL in children. Furthermore, many traditional AL biomarkers may not be appropriate for younger age groups given their developmental stage. Thus, validating the use of a biomarker of AL that is objective;distinct from disease or risk state;and can be collected longitudinally and noninvasively would represent a significant and innovative contribution to research on AL and health disparities. Telomere length is a known marker of the cellular aging process and a potential biomarker of AL that is truly cumulative, given increasing evidence linking psychosocial stress and shortened telomere length. The proposed research will take advantage of a unique opportunity to validate telomere length as a biomarker of AL among children using DNA samples already obtained from a community-based sample of 260 African American children ages 4 to 14 years from inner-city New Orleans, LA, U.S. neighborhoods whose cumulative risk and/or stress exposure can be characterized at the individual, household, school and neighborhood levels. This proposal will establish a longitudinal cohort that will allow tracking of telomere length and other AL biomarkers in relation to cumulative risk exposure derived from multiple levels (i.e., individual, household, school, and neighborhood). To accomplish our broad goal, we propose to address the following specific aims: 1) to establish an sex and age matched cohort of 260 children from 87 census tracts for which saliva and traditional AL markers as well as psychosocial and environmental measures of stress characterized at multiple levels (i.e. individual, household, and neighborhood) will be collected in the first year and combined with baseline data to include repeated samples of telomere length, for the first time, across a varied age range of children;2) to evaluate the validity of telomere length as a biomarker of AL. The longitudinal design will also permit exploration of whether earlier versus concurrent stress exposure and whether distal versus more proximal stress exposure are associated with telomere length changes. Results will offer methods through which we can begin to better understand, develop, and expand translational strategies to address and monitor biological risk and its impact on health outcomes, and at an early point in the life course. PUBLIC HEALTH RELEVANCE: Public Health Relevance: This proposal will track and validate physiologic biomarkers in relation to stress exposure derived from multiple levels (i.e., individual, household, school, and neighborhood) among African American children. Validating the use of a biomarker that is objective;distinct from disease or risk state;and can be collected longitudinally and noninvasively would represent a significant and innovative contribution to research on stress related studies and health disparities, allowing us to better understand, develop, and expand translational strategies to address and monitor biological risk and its impact on health outcomes, and at an early point in the life course.